CPC G16C 20/50 (2019.02) [C07K 1/04 (2013.01); C07K 14/70567 (2013.01); G16B 5/00 (2019.02); G16B 15/00 (2019.02); G16C 20/70 (2019.02)] | 3 Claims |
1. A method of identifying endocrine disrupting chemicals by determining whether a molecule of interest is a peroxisome proliferator-activated receptor γ full agonist, partial agonist or antagonist by analyzing a binding energy, the method comprising:
providing a simulated protein receptor mimicking said peroxisome proliferator-activated receptor γ and a simulation of the molecule of interest;
docking the simulation of the molecule of interest and the simulated protein receptor to form a docked conformation;
performing at least two rounds of molecular dynamic simulation to obtain at least one trajectory and at least one free energy surface, wherein one of the at least two rounds of molecular dynamic simulation comprises adopting a collective variable (CV) 1 and a CV2, wherein the CV1 is a first distance between Cα of Tyr473 on H12 and Cα of Leu453 on H11 of the peroxisome proliferator-activated receptor γ, and CV2 is a second distance between Cα of Tyr473 on H12 and Ca of Lys319 on H4 of the peroxisome proliferator-activated receptor γ;
inputting the trajectory to construct at least one pharmacophore and obtaining a binding energy diagram of the simulation of the molecule of interest docked on the simulated protein receptor; and
analyzing the binding energy diagram of simulation of the molecule of interest docked on the simulated protein in order to determine whether the molecule of interest is the peroxisome proliferator-activated receptor γ full agonist, partial agonist or antagonist;
wherein if the molecule of interest is a full agonist, the binding energy diagram shows one low energy area; and if the molecule of interest is an antagonist or a partial agonist, the binding energy diagram shows multiple low energy areas.
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